Asthma has long been known to run in families. More recently, linkage studies have been conducted to identify specific genes involved. However, this work has gone slowly with multiple regions of linkage being identified. It is clear that gene-environment interactions are important in determining who develops asthma. Linkage studies conducted to date have not been designed to properly explore interactions. Given the complex nature of asthma, it is clear that candidate gene association studies will be necessary to identify disease genes and interactions with environmental factors. The role of air pollution in asthma exacerbation has long been appreciated. Ozone, an oxidant air pollutant, is one of the agents that can worsen existing asthma. Recent data suggest that ozone and other air pollutants may play a role in asthma etiology, but there are few data. Recent linkage studies in animals are beginning to identify genes that are involved in specific physiologic responses to ozone and other inhaled pollutants. This project includes several studies the role of genetic polymorphisms, environmental factors and their interaction in the etiology of childhood respiratory disease. The primary project is a family study of genetic susceptibility to asthma in a highly ozone exposed population, Mexico City. This study uses the case-parent triad design. Although subject enrollment is still ongoing, we are starting to publish manuscripts from this study. Another component study is a cross-sectional examination of risk factors for respiratory disease among middle school students in Wuhan, China. In the past year, we have found that children with early life exposure to animals in the home are not at reduced risk of asthma, contrary to some reports in Western populations. However, in this Wuhan population, in which exposure to endotoxin and other bacterial products is high from other sources, this exposure is not protective. In another study, I am collaborating with Dr. Zeldin, investigators at UNC and engineers at a local company, Advanced Energy, to add onto a study that they will be beginning in FY2004. My addition will characterize airborne mold exposure in new homes fitted with features to reduce moisture levels and new homes built to existing building codes as well as older homes that subjects are moving out of. This work will provide important pilot data to justify a new study of health effects of fungal exposure in early life in North Carolina. I am also continuing development work on studies of early life factors in respiratory disease in Mexico City and am doing planning work to extend this study to local populations. This work was a separate ZO1 project in FY2003 (ES 44010). I am folding that project into this one for simplicity.